We have witnessed major improvements in our ability to detect and stage prostate cancer and have benefited from a sustained decrease in the death rate from this common disease due, in part, to the introduction of serum Prostate Specific Antigen (PSA) into clinical practice in the late 1970's. Now in 2004, in the wake of the "PSA era" discoveries, we continue to perform diagnostic biopsies unnecessarily on 75% of men with abnormal PSA levels, finding 1:4 with disease, we continue to understage nearly 30% of men with presumed localized disease, and we continue to lack additional clinically validated prostate cancer biomarkers. Also, as the "baby boomer" men reach their 60's, it is anticipated that the number of men over age 50 will increase greatly, reaching 80 million by year 2015. This, coupled with the fact that there are nearly 20 million men in the U.S. alone who have had one negative prostate biopsy yet still are risk for prostate cancer and can no longer rely on PSA as their biomarker of choice. Clearly further discovery, characterization and validation of potential biomarkers for the early detection of prostate cancer are greatly needed - The mission of the Early Detection Research Network. In this competitive renewal proposal we will outline our progress between 1999 and 2004 as an EDRN Clinical and Epidemiological Center. We will demonstrate our ability to accrue patients, archive an impressive and clinically valuable biorepository of specimens, take part in collaborative research within the EDRN network, Industry and non-EDRN investigators, actively take part in the governance of the EDRN and publish key biomarker findings. Within this renewal we will also outline our proposed continuation/enhancements of our biorepository, anticipated development and participation in validation studies, characterization of novel tumor markers (pre-validation), preliminary pilot studies of biomarkers, evaluation of biomarker technologies and development of multivariate tumor marker models for complex evaluation of multiple tumor markers.